Myelofibrosis

Myelofibrosis is a type of blood cancer known as a myeloproliferative neoplasm that is chronic and progressive in nature. It involves the abnormal development and function of bone marrow cells that produce blood cells and leads to the formation of scar tissue in the bone marrow. When the bone marrow becomes scarred it can’t make enough blood cells and this can cause anemia, enlargement of the spleen and liver, fatigue, and other problems. In some patients with myelofibrosis, the condition progresses to acute myeloid leukemia. Myelofibrosis is rare and affects ~ 18,000 people in the U. S. Although it can occur at any age it is most commonly occurs in individuals over 65.

When myelofibrosis develops on its own (and not as the result of another bone marrow disease), it’s called primary myelofibrosis. Myelofibrosis can also result from a worsening of other bone marrow diseases, such as polycythemia vera and essential thrombocythemia.

The following is a general overview of the diagnosis and treatment of myelofibrosis. Each person with myelofibrosis is different, and the specific characteristics of your condition will determine how it is managed. The information on this Web site is intended to help educate you about treatment options and to facilitate a shared decision-making process with your treating physician.

Symptoms of Myelofibrosis

In its early stages, myelofibrosis may not cause any symptoms. As the disease progresses, patients may experience the following symptoms which are the result of an enlarged spleen, abnormal blood cell production, and the release of too many cytokines into the blood.1:

Symptoms due to an enlarged spleen (splenomegaly):

Feeling pain or fullness below the ribs on the left side.

Feeling full sooner than normal when eating.

Pain under the left ribs.

Non-spleen related symptoms:

Feeling very tired.

Shortness of breath.

Easy bruising or bleeding.

Petechiae (flat, red, pinpoint spots under the skin that are caused by bleeding).

Bone/muscle pain

Itching

Night sweats.

Weight loss.

These symptoms can have a profound impact on quality of life.

Diagnosis of Myelofibrosis

Individuals diagnosed with myelofibrosis often have no symptoms. An enlarged spleen or an abnormal blood count may be noticed at a routine check up. Once a diagnosis is suspected additional tests or procedures that may be used to diagnose primary myelofibrosis include blood tests and a bone marrow examination 2. People with primary myelofibrosis often have low red blood cell counts (anemia) in addition to other blood cell abnormalities.

Roughly half of the people with primary myelofibrosis will test positive for a mutation in the Janus kinase 2 (JAK2) gene and the majority of individuals will have overactive JAK signaling even if the don’t have a JAK mutation. This abnormality can be measured by your doctor but doesn’t have to be present for a diagnosis. Increased production of JAK proteins causes the wrong number of blood cells and cytokines to be produced. An enlarged spleen may be detected on physical examination. Bone marrow examination typically reveals an increase in abnormal megakaryocytes (platelet-forming cells) and other abnormalities that are characteristic of myelofibrosis.

Slightly different criteria are used to diagnose myelofibrosis that develops after polycythemia vera or essential thrombocythemia 3.

Treatment of Myelofibrosis

Several characteristics of the patient and the myelofibrosis are used to assess a patient’s prognosis and treatment needs 2. Risk factors associated with a worse prognosis include:

Age over 65

Night sweats, fever, unintended weight loss

Anemia

Higher than normal levels of white blood cells

Higher than normal levels of immature (blast) blood cells

Lower than normal levels of platelets

Commonly used scoring systems for primary myelofibrosis consider these and assign a patient to one of four risk groups: low risk, intermediate-1 risk, intermediate-2 risk, or high-risk. Patients with low-risk primary myelofibrosis have a median survival of more than 15-years, whereas median survival in the high-risk patients is less than two years 4.

Depending on a patient’s individual situation, management of myelofibrosis may involve the following:

Close observation: Patients who have a low or intermediate-1 risk status and no symptoms or complications from myelofibrosis may not require immediate treatment.

Drug treatment: Drug treatment can help to manage the symptoms and complications of myelofibrosis. Drugs that may be used to treat myelofibrosis include the following:

Jakafi® (ruxolitinib): Approved in 2011, this is currently the only drug that has been approved specifically for myelofibrosis. Known as a JAK inhibitor, it is a targeted therapy that is intended for patients with intermediate- or high-risk myelofibrosis (including myelofibrosis that develops after polycythemia vera or essential thrombocythemia). Jakafi can help to relieve the signs and symptoms of myelofibrosis, such as enlargement of the spleen, night sweats, itching, and bone or muscle pain.

Androgens: Drugs that contain male hormones such as testosterone may be used to treat anemia.

Immunomodulators: drugs such as thalidomide or lenalidomide may also be used to treat anemia.

Chemotherapy: drug such as hydroxyurea can reduce spleen size and help to relieve myelofibrosis symptoms.

Corticosteroids: drugs such as prednisone can improve anemia in some patients.

Other drugs may also be used to manage symptoms and to reduce the occurrence or severity of complications from myelofibrosis.

Splenectomy or radiation to the spleen: Surgical removal of the spleen (splenectomy) or radiation to the spleen may be necessary if drug treatment doesn’t adequately manage spleen size and blood counts.

Stem cell transplantation: For carefully selected patients with high- or intermediate-risk myelofibrosis, an allogeneic stem cell transplant (ASCT) may be an option. ASCT is the only potentially curative treatment for myelofibrosis, but can produce life-threatening side effects. The procedure involves high doses of chemotherapy or radiation to destroy the unhealthy bone marrow. Blood-forming stem cells from a healthy, matched donor are then infused into the patient. A reduced-intensity allogeneic stem cell transplant may also be an option for some patients. This procedure uses lower doses of chemotherapy or radiation.

Management of Myelofibrosis that Progresses to Acute Myeloid Leukemia

In some patients with myelofibrosis, the condition progresses to a type of leukemia known as acute myeloid leukemia (AML). Information about the management of AML is available here.

Strategies to Improve Outcomes

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of myelofibrosis will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active investigation aimed at improving the treatment of myelofibrosis include the following 2:

Additional JAK inhibitors: The JAK inhibitor Jakafi was the first drug approved specifically for myelofibrosis, and other types of JAK inhibitors are being evaluated in clinical trials. JAK inhibitors may differ in their efficacy and side effects.

Pomalidomide: pomalidomide is an immunomodulatory drug that may improve blood cell counts. Certain patients may be more likely to derive a benefit than others, and researchers continue to evaluate predictors of response.

HDAC inhibitors: Other targeted drugs that are being evaluated for myeloproliferative neoplasms include histone deacetylase (HDAC) inhibitors. These drugs—which include givinostat, vorinistat, panobinostat, and others—interfere with enzymes that may contribute to cancer growth.

3 Barosi G, Mesa RA, Thiele J et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: A consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia. 2008;22:437-438.